rs2661280

Positions:

• chr1-163143585-G-C
• chr1-163143585-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003617.4(RGS5):​c.*3757C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 152,114 control chromosomes in the GnomAD database, including 46,779 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.78 (46779 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: RGS5 NM_003617.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488

Genes affected

RGS5 (HGNC:10001): (regulator of G protein signaling 5) This locus represents naturally occurring readthrough transcription between the neighboring LOC127814295 (uncharacterized LOC127814295) and RGS5 (regulator of G-protein signaling 5) genes on chromosome 1. Some variants of the readthrough transcript encode novel proteins with unique N-termini. [provided by RefSeq, Nov 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.866 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS5	NM_003617.4	c.*3757C>G		3_prime_UTR_variant	5/5	ENST00000313961.10	NP_003608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS5	ENST00000313961.10	c.*3757C>G		3_prime_UTR_variant	5/5	1	NM_003617.4	ENSP00000319308	P4
RGS5	ENST00000618415.4	c.*3757C>G		3_prime_UTR_variant	6/6	4		ENSP00000480891
RGS5	ENST00000469495.5	n.167+8965C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118839 AN: 151996 Hom.: 46762 Cov.: 31

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.779

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.782 AC: 118909 AN: 152114 Hom.: 46779 Cov.: 31 AF XY: 0.788 AC XY: 58606 AN XY: 74354

Gnomad4 AFR AF: 0.826

Gnomad4 AMR AF: 0.797

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.887

Gnomad4 SAS AF: 0.883

Gnomad4 FIN AF: 0.841

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.780

Alfa AF: 0.763 Hom.: 5253

Bravo AF: 0.776

Asia WGS AF: 0.863 AC: 3001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.5
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2661280; hg19: chr1-163113375;